Sulphur-containing 1,4-dihydropyridine derivatives

ABSTRACT

Sulphur-containing 1,4-dihydropyridine derivatives of the formula:   D R A W I N G WHEREIN R is hydrogen, saturated or unsaturated, straight, branched or cyclic alkyl of one to six carbon atoms, unsubstituted or substituted by hydroxyl or alkoxy of one to three carbon atoms, or benzyl or phenethyl unsubstituted or substituted in the aryl moiety by one, two or three members selected from the group consisting of one to three alkoxy moieties of one to three carbon atoms, one or two alkyl moieties of one to three carbon atoms and one to two halogen atoms, R&#39;&#39; is straight or branched chain alkyl of one to four carbon atoms, R&#39;&#39;&#39;&#39; is straight, branched, cyclic, saturated or unsaturated alkyl of one to six carbon atoms, said alkyl interrupted by one or two oxygen atoms or said alkyl substituted by hydroxyl, R&#39;&#39;&#39;&#39;&#39;&#39; is aryl substituted by SOnR1, unsubstituted or substituted by one to eight members selected from the group consisting of nitro, amino, acylamino of one to two carbon atoms, hydroxyl, acyloxy of one to two carbon atoms, one or two alkyl moieties of one to four carbon atoms, one or two alkoxy moieties of one to four carbon atoms, and one or two halogen atoms, N IS 0, 1, 2 OR 3, AND R1 is lower alkyl of one to four carbon atoms or phenyl when n is 0, 1 or 2 and R1 is hydrogen when n is 3, ARE USEFUL FOR THEIR CORONARY DILATING EFFECT AND ANTIHYPERTENSIVE EFFECTS. Processes for the production of these compounds are set forth below.

United States Patent 1 51 3,696,11 2 Bossert et al. 1 1 Oct. 3, 1972 SULPHUR-CONTAINING 1,4- the formula: H

DIHYDROPYRIDINE DERIVATIVES [72] v Inventors: Friedrich Bossert, Wuppertal-El- RHOOCW I COOR berfeld; Wulf Vater, Opladen, both of Germany it 73 A Farbenfabr'ken Ba r Akt'en llwherein 1 sslgnee chaft L vlrku a I gese R is hydrogen, saturated or unsaturated, straight, s e e ermany branched or cyclic alkyl of one to six carbon Flledi 20, 1970 atoms, unsubstituted or substituted by hydroxyl or alkoxy of one to three carbon atoms, or benzyl or [21] Appl' 9l607 phenethyl unsubstituted or substituted in the aryl moiety by one, two or three members selected [30] Foreign Application Priority Data from the group consisting of one to three alkoxy moieties of one to three carbon atoms, one or two 1969 Germany 19 63 1868 alkyl moieties of one to three carbon atoms and one to two halogen atoms, [52] Us. iS straight or branched chain alkyl of one to four 424/266 carbon atoms,

51 I t Cl and 31/50 R" is straight, branched, cyclic, saturated or unsatud Q94 8 F 6 rated alkyl of one to six carbon atoms, said alkyl 1e 0 earc interrupted by one or two Oxygen atoms or Said alkyl substituted by hydroxyl, [56] I References cued R is aryl substituted by SO R unsubstituted or UNITED STATES PATENTS substituted by one to eight members selected from the group consisting of nitro, amino, LOEV R acylamino of one to two carbon atoms hydroxyl, 3,441,648 4/1969 Loev et aL. ..260/295.5 R y y of one to two carbon atoms, one or two 3,455,939 7/1969 1 Loev et al ..260/294.8 F alkyl moieties of one to four carbon atoms, e or 3,455,945 7/1969 Loev.' ..260/295.5 R two alkoxy moieties of one to four carbon m 3,485,847 12/1969 Bossert et al ..260/295.5 R and one or two halogen atoms, 3,488,359 1/1970 Bossert et al ..260/295.5 R n 18 2 or nd 3,511,847 5/1970 Loev e161. ..260/295.5 R 1 is lower alkyl of one to four carbon atoms or Primary Examiner-Alan L. Rotman Att0rney-Jacobs & Jacobs ABSTRACT Sulphur-containing l,4-dihydropyridine derivatives of 23 Claims, N0 Drawings SULPHUR-CONTAINING 1,4-DIHYDROPYRIDINE DERIVATIVES The present invention is concerned with l,4-dihydropyridine derivatives. More particularly, the present invention is concerned with sulphur-containing 1,4- dihydropyridine derivatives of the formula:

wherein R is hydrogen, saturated or unsaturated, straight, branched or cyclic alkyl of one to six carbon atoms, unsubstituted or substituted by hydroxyl or alkoxy of one to three carbon atoms, or benzyl or phenethyl unsubstituted or substituted in the aryl moiety by one, two or three members selected from the group consisting of one to three alkoxy moieties of one to three carbon atoms, one or two 25 alkyl moieties of one to three carbon atoms and one or two halogen atoms, especially fluorine, chlorine or bromine,

R' is straight or branched chain alkyl of one to four carbon atoms,

R" is straight, branched, cyclic, saturated or unsaturated alkyl of one to six carbon atoms, said alkyl interrupted by one or two oxygen atoms or said alkyl substituted by hydroxyl,

R' is aryl substituted by SO,,R unsubstituted or substituted by one to eight members selected from the group consisting of nitro, amino, acylamino of one to two carbon atoms, hydroxyl, acyloxy of one to two carbon atoms, one or two alkyl moieties of one to four carbon atoms, one or two alkoxy moieties of one to four carbon atoms, and one or two halogen atoms, especially fluorine, chlorine or bromine,

nisO, l,2or3,and

R is lower alkyl of one to four carbon atoms or phenyl when n is 0, l or 2 and R is hydrogen when n is 3.

These compounds are especially useful for their coronary dilating effect and their antihypertensive effect, and when administered for these purposes, the compounds of the present invention are administered in the same general manner and amount as known coronary dilators and knownantihypertensives.

The compounds of the present invention may be produced by reacting an aldehyde of the formula:

R CHO wherein R' is as above defined, with an acyl-fatty acid ester of the formula:

wherein R and R" are as above defined, and ammonia or an amine of the formula:

5 2-methylsulphinyl-4-nitrobenzaldehyde,

or a salt thereof, wherein R is as above defined, or with an enamine of the formula:

wherein R, R and R" are as above defined, in organic solvents, such as alcohols, dioxane, glacial acetic acid, dimethylforrnamide, dimethylsulphoxide or acetonitrile or in water at elevated temperatures, preferably at the boiling point of the solvent.

When the compounds of the present invention are produced, wherein R is other than hydrogen, a preferred embodiment of the process, comprises carrying out the reaction in pyridine. This general process is described in German Pat. application No. P 19 23 990.8 which corresponds to US. application Ser. No. 35,574 filed May 7, 1970.

' It is further possible to produce the compounds of the present invention according to teachings set forth in Helv. Chim. Acta 41 (1958) 2066, by oxidizing 1,4- dihydropyridines, wherein R is hydrogen, with an oxidizing agent, quatemizing the resulting pyridine derivatives with alkyl esters and reducing these again with suitable reducing agents to 1,4-dihydropyridines.

The following specific compounds are representative but not exhaustive examples of the various reactants which can be used according to the present invention:

Aldehydes 2-, 3- or 4-methylmercaptobenzaldehyde, 2-, 3- or 4- ethylmercaptobenzaldehyde, 2-, 3- or 4-isopropylmercaptobenzaldehyde, 2-, 3- or 4-butylmercaptobenzaldehyde, 4-nitro-6-methylmercaptobenzaldehyde, 4- nitro-S-hydroxy-6-ethylmercaptobenzaldehyde, 2' phenylmercaptobenzaldehyde, 2-, 3- or 4-methylsulphinylbenzaldehyde, 2-, 3- or 4-methylsulphonylbenzaldehyde, 2-, 3- or 4-ethylsulphonylbenzaldehyde,

Z-methylsulphonyl-4-nitrobenzaldehyde, benzaldehyde-2- sulphonic acid, benzaldehyde-3-sulphonic acid, benzaldehyde-4-sulphonic acid, 3-nitrobenzaldehyde-2- sulphonic acid and 4-nitrobenzaldehyde-Z-sulphonic acid.

Acyl-fatty acid esters Fonnylacetic acid ethyl ester, formylacetic acid butyl ester, acetoacetic acid methyl ester, acetoacetic acid ethyl ester, acetoacetic acid propyl ester, acetoacetic acid isopropyl ester, acetoacetic acid butyl ester, acetoacetic acid (aor fl)-hydroxyethyl ester, acetoacetic acid (aor B)-methoxyethyl ester, acetoacetic acid (aor B)-ethoxyethyl ester, acetoacetic acid (aor B)-propoxyethyl ester, acetoacetic acid furfuryl ester, acetoacetic acid tetrahydrofurfuryl ester, acetoacetic acid ally] ester, acetoacetic acid propargyl ester, acetoacetic acid hexyl ester, propionyiacetic acid ethyl ester, butyrylacetic acid ethyl ester and isobutyrylacetic acid ethyl ester.

Amines Methylamine, ethylamine, propylamine, isopropylamine, butylamine, allylamine, propargylamine, l-hydroxyethylamine-2, l ,S-dihydroxyisopropylamine, cyclohexylamine, benzylamine, 4- chlorobenzylamine, 3,4-dimethoxybenzylamine and phenethylamine.

According to a preferred embodiment of the present invention, R is hydrogen, alkyl of one to six carbon atoms and especially one to three carbon atoms, alkyl of one to six carbon atoms substituted by hydroxyl and especially alkyl of one to three carbon atoms substituted by hydroxyl, or benzyl, R" is alkyl of one to six carbon atoms, and especially of one to three carbon atoms, alkenyl of two to six carbon atoms, and especially two or three carbon atoms, alkinyl of two to six carbon atoms, and especially two or three carbon atoms, or alkyl of one to six carbon atoms substituted by hydroxyl, especially alkyl of one to three carbon atoms substituted by hydroxyl, R' is phenyl S0,,R unsubstituted or substituted by a member selected from the group consisting of nitro, amino, acylamino of one to two carbon atoms, hydroxyl, acyloxy of one to two carbon atoms, one or two alkyl moieties of one to four carbon atoms, one or one alkoxy moieties of one to four carbon atoms, and one or two halogen atoms, and especially nitro, n is O, 1, 2 or 3 and R is alkyl of one to four carbon atoms, and especially methyl when n is 0, l or 2 and R is hydrogen when n is 3.

The compounds of the present invention are particularly useful by virtue of the below set forth effects demonstrated in in vivo animal tests:

1. On parenteral, oral and perlingual administration, the compounds effect a distinct and long-lasting dilation of the coronary vessels. This effect on the coronary vessels in intensified by a simultaneous nitrite-like heart-relieving effect.

They influence and/or modify the heart metabolism in the sense of a saving of energy. 2. The excitability of the stimulus-forming and excitation-conducting system within the heart is reduced, so that an anti-fluttering effect demonstrable in therapeutic doses results.

3. The tone of the smooth muscle of the vessels is greatly reduced under the action of the compounds. This vascular-spasmolytic action can occur in the entire vascular system or can manifest itself to a more or less isolated extend in circumscribed vascular regions (such as for example the central nervous system).

4. The compounds reduce the blood pressure of normal tonic and hypertonic animals and can thus be used as anti-hypertensive agents.

5. The compounds possess strong muscular-spasmolytic actions, which manifest themselves on the smooth muscle of the gastric and intestinal tract, the urogenital tract and the respiratory system.

The following non-limitative examples more particularly illustrate the present invention.

EXAMPLE 1 2,6-Dimethyl-4-(2-methylmercaptophenyl)-1,4- dihydropyridine-3,S-dicarboxylic acid dimethyl ester 6 g of Z-methylmercaptobenzaldehyde together with 10 ccs. of acetoacetic acid methyl ester and ccs. of

ammonia in 60 ccs. of methanol are heated to the boil for several hours, the mixture is filtered after addition of charcoal, and after cooling and filtering off, white crystals (9 g) of melting point 178 (methanol) are obtained.

The following compounds were produced in an analogous manner:

a. 2,6-dimethy1-4-(4-methylmercaptophenyl )-l ,4-

dihydropyridine-3,5-dicarboxy1ic acid dimethyl ester of melting point 174 to 176 C.

2,6-dimethyl-4-( 2 '-methylsu1phiny1phenyl )-l ,4- dihydropyridine-3,S-dicarboxylic acid dimethyl ester of melting point 280 C.

c. 2,6-dimethy1-4-(2'-methy1su1phonylpheny1)-l ,4-

dihydropyridine-3,S-dicarboxylic acid dimethyl ester of melting point 272 C.

d. 2,6-dimethyl-4-(2'-methylsulphony1phenyl)-1,4-

dihydropyridine-3,S-dicarboxylic acid diethyl ester of melting point 232 C.

e. 2,6-dimethyl-4-(4'-methylsu1phonylphenyl)-1 ,4-

dihydropyridine-3,5-dicarboxylic acid dimethyl ester of melting point 228 C.

f. 2,6-dimethyl-4-(3-nitro-4'-methylmercaptophenyl )-1 ,4-dihydropyridine-3,S-dicarboxylic acid dimethyl ester of melting point 202 C.

g. 2,6-dimethyl-4-(3'-nitro-6'-methylmercaptophenyl)-l ,4-dihydropyridine-3 ,S-dicarboxylic acid dimethyl ester of melting point 177 C.

h. 2,6-dimethyl-4-(2'-methylmercaptophenyl)-1 ,4-

dihydropyridine-3,S-dicarboxylic acid diallyl ester (oil).

EXAMPLE 2 l,2,6-Trimethyl-4-(4'-methylsulphony1phenyl)- 1 ,4- dihydropyridine-3,S-dicarboxylic acid dimethyl ester 10 g of 4-methylsulphonylbenzaldehyde, l2 ccs. of acetoacetic acid methyl ester and 4 g of methylamine hydrochloride in 30 ccs. of pyridine are heated to approx. C for 1 to 2 hours. After pouring into water, the product is filtered off, washed with water and recrystallized from 500 ccs. of methanol. Light yellow crystals 16 g) of melting point 188 C are obtained.

The following compounds were produced in an analogous manner:

a. 1,2,6-trimethyl-4-(4-methylmercaptophenyl 1 ,4-dihydropyridine-3,S-dicarboxylic dimethyl ester, melting point C.

1,2,6-trimethy1-4-( 2 '-methylmercaptopheny1 1 ,4-dihydropyridine-3 ,S-dicarboxylic acid dimethyl ester of melting point 125 C. c. 1 ,2,6-trimethy1-4-(4'-methy1mercaptophenyl 1 ,4-dihydropyridine-3,S-dicarboxylic acid di-(B- ethoxyethyl ester); oil.

1,2,6-trimethyl-4-( 3 '-nitro-4-methylmercaptopheny1)- 1 ,4-dihydropyridine-3,S-dicarboxylic acid dimethyl ester of melting point 131 C. e. l,2,6-trimethy1-4-( 2 -mercaptopheny1)-1 ,4-

dihydropyridine-3,S-dicarboxylic acid dipropargyl ester of melting point 86 C.

acid

EXAMPLE 3 A solution of 18.5 g of benzaldehyde-4-sulphonic acid, 26 ccs. of acetoacetic acid ethyl ester and 22 ccs. of ammonia in 250 ccs. of alcohol is heated overnight to the boil, and after cooling the product is filtered off and yields light yellow crystals (20 g) of melting point EXAMPLE 4 2,6-Dimethyl-4-(4'-methylmercaptophenyl)- l ,4- dihydropyridine-3,S-dicarboxylic acid di-(B- ethoxyethyl ester) 7.5 cos. of 4-methylmercaptobenzaldehyde, ccs. of acetoacetic acid B-ethoxyethyl ester and 5 ccs. of ammonia in 50 ccs. of ethanol are heated to the boil for several hours, after adding animal charcoal the mixture is filtered, and the filtrate is evaporated in vacuo. Purification via ether. Oil; 23 g.

EXAMPLE 5 l-Benzyl-2,6-dimethyl-4-(4'-mercaptophenyl )-l ,4- dihydropyridine-3,S-dicarboxylic acid dimethyl ester l4 g of 4-methylmercaptobenzaldehyde, 25 ccs. of acetoacetic acid methyl ester and 10 ccs. of benzylamine in cos. of pyridine are heated for 5 hours to 90l00 C, the mixture is introduced into ice water and after some hours the product is filtered off. White crystals (16 g) of melting point 160 C (methanol).

The following compound was produced in an analogous manner:

a. l-B-hydroxyethyl-2,6-dimethyl-4-(4'-methylmercaptophenyl)- l ,4-dihydropyridine-3,S-dicarboxylic acid dimethyl ester of melting point 158 C.

The present invention also includes pharmaceutical compositions which comprise one of the above set forth compounds according to the present invention in combination with a pharmaceutically acceptable nontoxic inert diluent or carrier. Said pharmaceutical compositions are made according to the techniques which are per se well known in the art. Any of the usual carriers, diluents, excipients and the like may be utilized according to standard techniques. Such tablets, capsules, dragees, solutions, suspensions and the like form part of the present invention. Also a part of the present invention is the method of effecting coronary action in humans and animals which comprises administering to a human or animal in need thereof a therapeutically effective amount of a compound of the present invention until amelioration of the condition occurs.

What is claimed is:

l. A sulphur-containing 1,4-dihydropyridine derivative of the formula:

R"O O C C 0 0R" R! i I RI wherein R is hydrogen, saturated or unsaturated, straight, branched or cyclic alkyl of one to six carbon atoms, unsubstituted or substituted by hydroxyl or alkoxy of one to three carbon atoms, or benzyl or phenethyl unsubstituted or substituted in the aryl moiety by l, 2 or 3 members selected from the group consisting of one to three alkoxy moieties of one to three carbon atoms, one or two alkyl moieties of one to three carbon atoms and one or two halogen atoms,

R is straight or branched chain alkyl of one to four carbon atoms,

R" is straight, branched, cyclic, saturated or unsaturated alkyl of one to six carbon atoms, said alkyl interrupted by one or two oxygen atoms or said alkyl substituted by hydroxyl,

R' is phenyl substituted by SO,,R unsubstituted or substituted by one or two members selected from the group consisting of nitro, amino, acylamino of one to two carbon atoms, hydroxyl, acyloxy of one to two carbon atoms, one or two alkyl moieties of one to four carbon atoms, one or two alkoxy moieties of one to four carbon atoms, and one or two halogen atoms,

nisO, 1,2or 3,and

R is lower alkyl of one to four carbon atoms or phenyl when n is 0, l or 2 and R is hydrogen when n is 3.

2. A compound according to claim 1, wherein R is hydrogen, alkyl of one to six carbon atoms, alkyl of one to six carbon atoms substituted by hydroxyl, or benzyl,

R" is alkyl of one to six carbon atoms, alkenyl of two to six carbon atoms, alkinyl of two to six carbon atoms or alkyl of one to six carbon atoms substituted by hydroxyl,

R is phenyl S0,,R unsubstituted or substituted by a member selected from the group consisting of nitro, amino, acylamino of l to 2 carbon atoms, hydroxyl, acyloxy of one to two carbon atoms, one or two alkyl moieties of one to four carbon atoms, one or two alkoxy moieties of one to four carbon atoms and one or two halogen atoms,

nisO, 1,2or 3,and

R, is alkyl of one to four carbon atoms when n is 0, l

or 2 and R is hydrogen when n is 3.

3. The compound according to claim 1 which is 2,6- dimethyl-4-( 2'-methylmercaptophenyl l ,4- dihydropyridine-3,S-dicarboxylic acid dimethyl ester.

4. The compound according to claim 1 which is 2,6- dimethyl-4-(4'-methylmercaptophenyl )-l ,4- dihydropyridine-3,S-dicarboxylic acid dimethyl ester.

5. The compound according to claim 1 which is 2,6- dimethyl-4-( 2'-methylsulphinylphenyl)- l ,4- dihydropyridine-3,S-dicarboxylic acid dimethyl ester.

6. The compound according to claim 1 which is 2,6- dimethyl-4-( 2'-methylsulphonylphenyl l ,4- dihydropyridine-3,S-dicarboxylic acid dimethyl ester.

7. The compound according to claim 1 which is 2,6- dimethyl-4-( 2'-methylsulphonylphenyl)- l ,4- dihydropyridine-3,S-dicarboxylic acid diethyl ester.

8. The compound according to claim 1 which is 2,6- dimethyl-4-(4'-methylsulphonylphenyl)- l ,4- dihydropyridine-3,S-dicarboxylic acid dimethyl ester.

9. The compound according to claim 1 which is 2,6- dimethyl-4-( 3 '-nitro-4-methylmercaptophenyl l ,4- dihydropyridine-3,S-dicarboxylic acid dimethyl ester.

10. The compound according to claim 1 which is 2,6- dimethyl-4-( 3'-nitro-6'-methylmercaptophenyl)-l ,4- dihydropyridine-3,S-dicarboxylic acid dimethyl ester.

11. The compound according to claim 1 which is 2,6- dimethyl-4-( 2'-methylmercaptophenyl)- l ,4- dihydropyridine-3,S-dicarboxylic acid diallyl ester.

12. The compound according to claim 1 which is l ,2,6-trimethyl-4-(4-methylsulphonylphenyl)-l ,4- dihydropyridine-3,5-dicarboxylic acid dimethyl ester.

13. The compound according to claim 1 which is l ,2,6-trimethyl-4-(4'-methylmercaptophenyl)-1,4- dihydropyridine-3,S-dicarboxylic acid dimethyl ester.

14. The compound according to claim 1 which is l ,2,6-trimethyl-4-(2'-methylmercaptophenyl)- l ,4- dihydropyridine-3,S-dicarboxylic acid dimethyl ester.

15. The compound according to claim 1 which is l,2,6-trimethyl-4-(4'-methylmercaptophenyl)-l ,4- dihydropyridine-3,S-dicarboxylic acid di-(B-ethoxyethyl ester).

16. The compound according to claim 1 which is l,2,6-trimethyl-4-( 3 '-nitro-4'-methylmercaptophenyl l,4-dihydropyridine-3,S-dicarboxylic acid dimethyl ester.

17. The compound according to claim 1 which is l ,2,6-trimethyl-4-( 2-mercaptophenyl)- l ,4- dihydropyridine-3,S-dicarboxylic acid dipropargyl ester.

18. The compound according to claim 1 which is 2,6- dimethyl-4-(4-sulphonyl)- l ,4-dihydropyridine-3,5- dicarboxylic acid diethyl ester.

19. The compound according to claim 1 which is 2,6- dimethyl-4-( 3 '-nitro-6'-sulphophenyl )-l ,4- dihydropyridine-3,S-dicarboxylic acid diethyl ester.

20. The compound according to claim 1 which is 2,6- dimethyl-4-(4-nitro-6-sulphophenyl)- l ,4- dihydropyridine-3,S-dicarboxylic acid diethyl ester.

21. The compound according to claim 1 which is 2,6- dimethyl-4-(4-methylmercaptophenyl )-l ,4- dihydropyridine-3,S-dicarboxylic acid di-(fi-ethoxyethyl ester).

22. The compound according to claim 1 which is lbenzyl-2,6-dimethyl-4-(4'-mercaptophenyl l ,4- dihydropyridine-3,5-dicarboxylic acid dimethyl ester.

23. The compound according to claim 1 which is l- B-hydroxyethyl-2,6-dimethyl-4-(4'-methylmercaptophenyl l ,4-dihydropyridine-3,S-dicarboxylic dimethyl ester.

acid 

2. A compound according to claim 1, wherein R is hydrogen, alkyl of one to six carbon atoms, alkyl of one to six carbon atoms substituted by hydroxyl, or benzyl, R'''' is alkyl of one to six carbon atoms, alkenyl of two to six carbon atoms, alkinyl of two to six carbon atoms or alkyl of one to six carbon atoms substituted by hydroxyl, R'''''' is phenyl SOnR1 unsubstituted or substituted by a member selected from the group consisting of nitro, amino, acylamino of 1 to 2 carbon atoms, hydroxyl, acyloxy of one to two carbon atoms, one or two alkyl moieties of one to four carbon atoms, one or two alkoxy moieties of one to four carbon atoms and one or two halogen atoms, n is 0, 1, 2 or 3, and R1 is alkyl of one to four carbon atoms when n is 0, 1 or 2 and R1 is hydrogen when n is
 3. 3. The compound according to claim 1 which is 2,6-dimethyl-4-(2''-methylmercaptophenyl)-1,4-dihydropyridine-3,5 -dicarboxylic acid dimethyl ester.
 4. The compound according to claim 1 which is 2,6-dimethyl-4-(4''-methylmercaptophenyl)-1,4-dihydropyridine-3,5 -dicarboxylic acid dimethyl ester.
 5. The compound according to claim 1 which is 2,6-dimethyl-4-(2''-methylsulphinylphenyl)-1,4-dihydropyridine-3,5 -dicarboxylic acid dimethyl ester.
 6. The compound according to claim 1 which is 2,6-dimethyl-4-(2''-methylsulphonylphenyl)-1,4-dihydropyridine-3,5 -dicarboxylic acid dimethyl ester.
 7. The compound according to claim 1 which is 2,6-dimethyl-4-(2''-methylsulphonylphenyl)-1,4-dihydropyridine-3,5 -dicarboxylic acid diethyl ester.
 8. The compound according to claim 1 which is 2,6-dimethyl-4-(4''-methylsulphonylphenyl)-1,4-dihydropyridine-3,5 -dicarboxylic acid dimethyl ester.
 9. The compound according to claim 1 which is 2,6-dimethyl-4-(3''-nitro-4''-methylmercaptophenyl)-1,4-dihydropyridine-3,5 -dicarboxylic acid dimethyl ester.
 10. The compound according to claim 1 which is 2,6-dimethyl-4-(3''-nitro-6''-methylmercaptophenyl)-1,4-dihydropyridine-3,5 -dicarboxylic acid dimethyl ester.
 11. The compound according to claim 1 which is 2,6-dimethyl-4-(2''-methylmercaptophenyl)-1,4-dihydropyridine-3,5 -dicarboxylic acid diallyl ester.
 12. The compound according to claim 1 which is 1,2,6-trimethyl-4-(4''-methylsulphonylphenyl)-1,4-dihydropyridine-3,5 -dicarboxylic acid dimethyl ester.
 13. The compound according to claim 1 which is 1,2,6-trimethyl-4-(4''-methylmercaptophenyl)-1,4-dihydropyridine-3,5 -dicarboxylic acid dimethyl ester.
 14. The compound according to claim 1 which is 1,2,6-trimethyl-4-(2''-methylmercaptophenyl)-1,4-dihydropyridine-3,5 -dicarboxylic acid dimethyl ester.
 15. The compound according to claim 1 which is 1,2,6-trimethyl-4-(4''-methylmercaptophenyl)-1,4-dihydropyridine-3,5 -dicarboxylic acid di-( Beta -ethoxyethyl ester).
 16. The compound according to claim 1 which is 1,2,6-trimethyl-4-(3''-nitro-4''-methylmercaptophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid dimethyl ester.
 17. The compound according to claim 1 which is 1,2,6-trimethyl-4-(2''-mercaptophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid dipropargyl ester.
 18. The compound according to claim 1 which is 2,6-dimethyl-4-(4''-sulphonyl)-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester.
 19. The compound according to claim 1 which is 2,6-dimethyl-4-(3''-nitro-6''-sulphophenyl)-1,4-dihydropyridine-3,5 -dicarboxylic acid diethyl ester.
 20. The compound according to claim 1 which is 2,6-dimethyl-4-(4''-nitro-6''-sulphophenyl)-1,4-dihydropyridine-3,5 -dicarboxylic acid diethyl ester.
 21. The compound according to claim 1 which is 2,6-dimethyl-4-(4''-methylmercaptophenyl)-1,4-dihydropyridine-3,5 -dicarboxylic acid di-( Beta -ethoxyethyl ester).
 22. The compound according to claim 1 which is 1-benzyl-2,6-dimethyl-4-(4''-mercaptophenyl)-1,4-dihydropyridine-3,5 -dicarboxylic acid dimethyl ester.
 23. The compound according to claim 1 which is 1- Beta -hydroxyethyl-2,6-dimethyl-4-(4''-methylmercaptophenyl)-1,4-dihydropyridine -3,5-dicarboxylic acid dimethyl ester. 